The NCX and NCKX exchangers share sequence similarity in the transport a-repeat domains: GSAPE within the a1 repeat, and GTSPD within the a2 repeat. The CCX exchanger has a unique conserved sequence within the a-repeats: GNGPD in a1 and SxGD in a2. Three NCX genes, five NCKX genes, and one CCX gene have been cloned and identified in mammals. Mammalian NCXs are highly expressed in cardiac muscle, skeletal muscle, and the central nervous system. Mammalian NCKX1-5 are widely expressed in various cells including rod and cone photoreceptor cells, retinal ganglion cells, platelets, vascular smooth muscles, uterus, brain tissue, intestine, lungs, thymus, and epidermal cells. The mammalian CCX exchanger NCLX is expressed in all tissues examined including the brain, thymus, heart, skeletal muscles, lungs, kidneys, intestines and testes and has been shown to localize to mitochondria. Furthermore, searching more nematode genomes as they become more annotated will add more resolution to the timing of gene accretion within the NCLX subtype by also testing the alternative possibility that these NCLXtype duplicates may have been lost in other nematode lineages. It was also surprising that we did not detect NCLX-type orthologs within the genomes of the Clade III nematodes that we examined. Gene loss is one possibility to explain this observation, however, it is unexpected considering the central role NCLX proteins have been shown to play in mammalian systems. Alternative Pazopanib molecular weight hypotheses include, diversification or low sequence coverage, each of these scenarios may have precluded their detection using our approach, and further annotation and functional analysis will be required to resolve these questions. NCX4 has been found exclusively in teleost, amphibian, and reptilian genomes and is not present in mammalian genomes, and interestingly NCX4 is thought to have been lost from the mammalian genome. NCX4 has been shown to function as an NCX-type exchanger, and in zebrafish is ubiquitously expressed with highest levels in the brain and eyes. Reduction of NCX4 activity by morpholinos in zebrafish embryos has been shown to affect left-right patterning causing heterotaxia, situs inversus, as well as reversed cardiac looping. These data demonstrate that functional specializations within the NCX family can vary significantly across species. Understanding this family of proteins means also understanding differences within this family, and an entry point into this problem is using comparative genomics to resolve structural and taxonomic specializations. Identifying nutritional strategies to alleviate the obesity pandemic are of great interest. Diet-induced thermogenesis, i.e. the regulated liberation of energy in the form of heat, could lower food efficiency, and thereby diminish obesity development. Already in 1939, induction of adaptive thermogenesis by feeding rats very low or very high protein diets was described. Later, the increment in thermogenesis by low-protein diets was verified in rats, in baby pigs, and similar effects were observed in young human subjects. Thus, intake of LP diets induces thermogenesis, but instead of resulting in decreased body mass, the reduced food efficiency is compensated for by a higher food intake.